Certain malignant tumors are known to be associated with increased collaganese activities that may be specific in their degradation of interstitial and basement membrane collagens. The responsible enzymes, which appear to resemble other mammalian tissue collagenases, may give the tumor a special capacity for invasiveness and metastasis. Evidence has been obtained with C3HBA adenocarcinoma showing that retinoic acid inhibits the production of interstitial collagen-directed collagenase activity in primary stromal cultures obtained from tumor tissues, and that vitamin A prevents tumor metastasis and invasion with an increase in the size of the tumor. These results are consistent with decreased degradation of collagen barriers. Since collagenases thus might have important functions in neoplastic proliferation, we will study the inhibitory effects of vitamin A and dexamethasone, a known inhibitor of collagenase synthesis, on the production of tumorassociated collagenases and other proteases in relation to tumor invasion and metastasis. In these studies we shall use the mouse model, C3HBA adenocarcinoma, which is known to be a highly metastatic tumor. We shall determine whether its invasiveness is related to the collagenases and proteases, both in terms of distribution of the enzymes in relation to the tumors and in terms of possible coordinate appearance of the enzyme activities in relation to the invasive processes in the tissues. For those studies we shall employ radiolabeled substrates for assays of enzyme activities and radioimmunoassays for determination of actual enzyme levels. We also shall determine whether the production of collagens and collagenase inhibitors is increased in tumor-borne animals treated with vitamin A and dexamethasone, and seek possible relationships among levels of leukopoiesis, diminished metastasis and collagen deposition in the tumors. This research may contribute to an understanding of some aspects of tumor invasion and metastasis, and may suggest means by which to suppress or control those processes.